First-episode psychosis and white matter 10 years later: what have we learned? A literature review update

Psychosis is a psychiatric disorder causing the loss of contact with reality. First-episode psychosis (FEP) represents the initial manifestation of psychotic symptoms. The pathophysiology of FEP is characterized by several neurobiological alterations, including microstructural damages within white matter (WM) tissues. In particular, reduced fractional anisotropy (FA) and increased mean diffusivity were reported in several brain regions underlying a widespread disruption in WM integrity. Over the last decade the massive employment of tract-based spatial statistics and tractography, two analysis techniques based on diffusion tensor imaging (DTI), provided new insights on the microstructural damages in FEP. Therefore, our aim was to provide a literature review update covering the last ten years of research. Record research was conducted from January 1, 2014, to November 24, 2023, across three datasets: PubMed, Scopus and Web of Science. Eleven studies were selected. Overall, WM disruptions were predominantly observed in corpus callosum, superior longitudinal fasciculus, and cingulum. Specifically, within these brain regions, decreased FA suggested alterations in WM integrity linked to the loss of tissue density and axonal fibers. Furthermore, structural modifications of WM microstructure could explain impairments in high-order cognitive functions, such as working memory and verbal processing, as well as positive symptoms of psychosis, including delusions. However, the reviewed studies have some limitations, including sample heterogeneity according to psychosis diagnosis, pharmacological treatment, and limited investigation of DTI indices. Therefore, future research is demanded to mitigate the confounding effects of psychosis diagnosis and improve DTI analysis to better discriminate against the neurobiological markers characterizing FEP.